Properties of Cryptic Epitopes and Their Corresponding Antibodies as Indicated by the Study of Human and Ovine Growth Hormones

M. E. LOUREIRO; V. J. MARINO; P. A. MATHIEU; M. DUHALDE; L. P. ROGUIN; C. PEÑA; L. A. RETEGUI

IMMUNOLOGICAL INVESTIGATIONS

Informa Healthcare

Año: 2007 vol. 36 p. 159 - 179

0882-0139

Antibodies (Ab) directed to hidden antigenic determinants (cryptotopes) are undesirablebecause they are not neutralizing. Additionally, we have previously demonstrateda close association between the extent of Ab to cryptic determinants and the expressionof autoantibodies (autoAb) under some experimental conditions. Thus, the first objectiveof this work was to establish the physicochemical characteristics of Ab to cryptotopesand the second one was to examine the structural features of cryptic epitopesthemselves. Using human and ovine growth hormones (hGH and oGH) as antigenicmodels and competition ELISA under different conditions of temperature, pH or ionicstrength, we did not find any difference between the binding properties of anti-crypticepitope antibodies (Ab) and anti-native epitope Ab. Then, using synthetic peptides andtryptic digests and direct and competition ELISAs we studied the structures of cryptichGH and oGH epitopes. Isolated peptides either in solution or adsorbed on microplatesfailed to react. Partially digested hGH was recognized only when insolubilized onmicroplates, and anti-oGH Ab only reacted with a large fragment of the hormone eitherin solution or insolubilized. These results indicate that, at least in the case of hGH andoGH, cryptic epitopes are not simple linear sequences, as commonly referred withoutany evidence, but new exposed conformational structures different from those found inthe native antigen.